Organ transplantation has become an accepted modality for the treatment of end-stage organ failure. The field of transplant medicine has made tremendous strides within the last thirty years, allowing for newer, more potent immunosuppressive medications rendering acute rejection episodes less frequent and less aggressive. In spite of these accomplishments, chronic allograft dysfunction (CAD) remains a leading cause of graft loss in the long term. Various translational research efforts have identified pathways and potential therapeutics that may allay the effects of CAD by conferring a tolerogenic phenotype in allograft recipients both in mouse and man.
Cellular therapies including regulatory T cells (Treg) have garnered attention in the literature for their natural and adaptive ability to suppress allo-immune responses and provide long-term graft survival in various mouse and humanized experimental models. Harnessing the ability of various regulatory-type cells to confer a tolerogenic phenotype is under vigorous translational and clinical investigations at present, and is now in the early stages of clinical trials. Additionally, the protective ability of Treg may be bolstered by the use of pharmaco-therapeutics such as rapamycin, which selectively allows for the proliferation of Treg while inhibiting the growth of effector T cells. When combined, sub-therapeutic doses of both therapies have been shown to successfully attenuate transplant arteriosclerosis, a pathognomonic hallmark of chronic rejection, in humanized mouse models. Despite these data, rapamycin continues to be used only sparingly in the peri-operative period due to various deleterious systemic effects of poor wound healing, proteinuria, hyperlipidemia, and poor patient tolerance, to name a few.